Faculty Bibliography

PURPOSE/OBJECTIVE:In critical illness, the relation between the macrocirculation, microcirculation and organ dysfunction, such as acute kidney injury (AKI), is complex. This study aimed at identifying predictors for AKI in patients with cardiogenic shock. MATERIALS AND METHODS/METHODS:, and whose microcirculation was measured within 48 h were enrolled. Patient data were analyzed if AKI stage ≥1 developed according to the Kidney Disease/Improving Outcomes classification within 48 h after admission. Variables with a p < .05 in the univariate analysis were considered for analysis with logistic regression. RESULTS:Twenty-four patients (61.5%) developed AKI within 48 h. The group that developed AKI had higher central venous pressures (CVP), lower diastolic arterial blood pressures and mean perfusion pressures, higher maximum ventilator pressures as well as positive end expiratory pressures and were treated with higher dosages of dobutamine. There was no difference of the microcirculation. In the multivariate logistic regression analysis, CVP was the only independent predictor for AKI (OR 1.241; 95% CI 1.030-1.495; p = .023). CONCLUSIONS:In this population of patients with cardiogenic shock, CVP was associated with the development of AKI.

In critically ill patients, it is frequently challenging to identify who will benefit from admission to the intensive care unit and life-sustaining interventions when the chances of a meaningful outcome are unclear. In addition, the acute illness not only affects the patients but also family members or surrogates who often are overwhelmed and unable to make thoughtful decisions. In these circumstances, a time-limited trial (TLT) of intensive care treatment can be helpful. A TLT is an agreement to initiate all necessary treatments or treatments with clearly delineated limitations for a certain period of time to gain a more realistic understanding of the patient's chances of a meaningful recovery or to ascertain the patient's wishes and values. In this article, we discuss current research on different aspects of TLTs in the intensive care unit. We propose how and when to use TLTs, discuss how much time should be taken for a TLT, give an overview of the potential impact of TLTs on healthcare resources, describe ethical challenges concerning TLTs, and discuss how to evaluate a TLT.

BACKGROUND:ANDROMEDA-SHOCK is an international, multicenter, randomized controlled trial comparing peripheral perfusion-targeted resuscitation to lactate-targeted resuscitation in patients with septic shock in order to test the hypothesis that resuscitation targeting peripheral perfusion will be associated with lower morbidity and mortality. OBJECTIVE:To report the statistical analysis plan for the ANDROMEDA-SHOCK trial. METHODS:We describe the trial design, primary and secondary objectives, patients, methods of randomization, interventions, outcomes, and sample size. We describe our planned statistical analysis for the primary, secondary and tertiary outcomes. We also describe the subgroup and sensitivity analyses. Finally, we provide details for presenting our results, including mock tables showing baseline characteristics, the evolution of hemodynamic and perfusion variables, and the effects of treatments on outcomes. CONCLUSION/CONCLUSIONS:According to the best trial practice, we report our statistical analysis plan and data management plan prior to locking the database and initiating the analyses. We anticipate that this procedure will prevent analysis bias and enhance the utility of the reported results.

While the pulmonary artery catheter (PAC) is still interesting in specific situations, there are many alternatives. A group of experts from different backgrounds discusses their respective interests and limitations of the various techniques and related measured variables. The goal of this review is to highlight the conditions in which the alternative devices will suffice and when they will not or when these alternative techniques can provide information not available with PAC. The panel concluded that it is useful to combine different techniques instead of relying on a single one and to adapt the "package" of interventions to the condition of the patient. As a first step, the clinical and biologic signs should be used to identify patients with impaired tissue perfusion. Whenever available, echocardiography should be performed as it provides a rapid and comprehensive hemodynamic evaluation. If the patient responds rapidly to therapy, either no additional monitoring or pulse wave analysis (allowing continuous monitoring in case potential degradation is anticipated) can be applied. If the patient does not rapidly respond to therapy or complex hemodynamic alterations are observed, pulse wave analysis coupled with TPTD is suggested.

BACKGROUND:Septic shock is a highly lethal condition. Early recognition of tissue hypoperfusion and its reversion are key factors for limiting progression to multiple organ dysfunction and death. Lactate-targeted resuscitation is the gold-standard under current guidelines, although it has several pitfalls including that non-hypoxic sources of lactate might predominate in an unknown proportion of patients. Peripheral perfusion-targeted resuscitation might provide a real-time response to increases in flow that could lead to a more timely decision to stop resuscitation, thus avoiding fluid overload and the risks of over-resuscitation. This article reports the rationale, study design and analysis plan of the ANDROMEDA-SHOCK Study. METHODS:ANDROMEDA-SHOCK is a randomized controlled trial which aims to determine if a peripheral perfusion-targeted resuscitation is associated with lower 28-day mortality compared to a lactate-targeted resuscitation in patients with septic shock with less than 4 h of diagnosis. Both groups will be treated with the same sequential approach during the 8-hour study period pursuing normalization of capillary refill time versus normalization or a decrease of more than 20% of lactate every 2 h. The common protocol starts with fluid responsiveness assessment and fluid loading in responders, followed by a vasopressor and an inodilator test if necessary. The primary outcome is 28-day mortality, and the secondary outcomes are: free days of mechanical ventilation, renal replacement therapy and vasopressor support during the first 28 days after randomization; multiple organ dysfunction during the first 72 h after randomization; intensive care unit and hospital lengths of stay; and all-cause mortality at 90-day. A sample size of 422 patients was calculated to detect a 15% absolute reduction in mortality in the peripheral perfusion group with 90% power and two-tailed type I error of 5%. All analysis will follow the intention-to-treat principle. CONCLUSIONS:If peripheral perfusion-targeted resuscitation improves 28-day mortality, this could lead to simplified algorithms, assessing almost in real-time the reperfusion process, and pursuing more physiologically sound objectives. At the end, it might prevent the risk of over-resuscitation and lead to a better utilization of intensive care unit resources. Trial registration ClinicalTrials.gov Identifier: NCT03078712 (registered retrospectively March 13th, 2017).

BACKGROUND AND OBJECTIVES: Working in an Intensive Care Unit (ICU) is increasingly complex and is also physically, cognitively and emotionally demanding. Although the negative emotions of work-related stress have been well studied, the opposite perspective of work engagement might also provide valuable insight into how these emotional demands may be countered. This study focused on the work engagement of ICU professionals and explored the complex relationship between work engagement, job demands and advantageous personal resources. METHODS: This was a cross-sectional survey study among ICU professionals in a single-centre university hospital. Work engagement was measured by the Utrecht Work Engagement Scale, which included items about opinions related to the respondent's work environment. Additionally, 14 items based on the Jefferson Scale of Physician Empathy were included to measure empathic ability. A digital link to the questionnaire was sent in October 2015 to a population of 262 ICU nurses and 53 intensivists. RESULTS: The overall response rate was 61% (n=193). Work engagement was negatively related both to cognitive demands among intensivists and to emotional demands among ICU nurses. No significant relationship was found between work engagement and empathic ability; however, agreeableness, conscientiousness, and emotional stability were highly correlated with work engagement. Only the number of hours worked per week remained as a confounding factor, with a negative effect of workload on work engagement after controlling for the effect of weekly working hours. CONCLUSION: Work engagement counterbalances work-related stress reactions. The relatively high workload in ICUs, coupled with an especially heavy emotional burden, may be acknowledged as an integral part of ICU work. This workload does not affect the level of work engagement, which was high for both intensivists and nurses despite the known high job demands. Specific factors that contribute to a healthy and successful work life among ICU professionals need further exploration.

Hyperlactatemia is a strong predictor of mortality in diverse populations of critically ill patients. In this article, we will give an overview of how lactate is used in the intensive care unit. We describe the use of lactate as a predictor of outcome, as a marker to initiate therapy and to monitor adequacy of initiated treatments.

INTRODUCTION: Acute circulatory dysfunction in patients with sepsis can evolve rapidly into a progressive stage associated with high mortality. Early recognition and adequate resuscitation could improve outcome. However, since the spectrum of clinical presentation is quite variable, signs of hypoperfusion are frequently unrecognized in patients just admitted to the emergency department (ED). Hyperlactatemia is considered a key parameter to disclose tissue hypoxia but it is not universally available and getting timely results can be challenging in low resource settings. In addition, non-hypoxic sources can be involved in hyperlactatemia, and a misinterpretation could lead to over-resuscitation in an unknown number of cases. Capillary refill time (CRT) is a marker of peripheral perfusion that worsens during circulatory failure. An abnormal CRT in septic shock patients after ICU-based resuscitation has been associated with poor outcome. The aim of this study was to determine the prevalence of abnormal CRT in patients with sepsis-related hyperlactatemia in the early phase after ED admission, and its relationship with outcome. METHODS: We performed a prospective observational study. Septic patients with hyperlactemia at ED admission subjected to an initial fluid resuscitation (FR) were included. CRT and other parameters were assessed before and after FR. CRT-normal or CRT-abnormal subgroups were defined according to the status of CRT following initial FR, and major outcomes were registered. RESULTS: Ninety-five hyperlactatemic septic patients were included. Thirty-one percent had abnormal CRT at ED arrival. After FR, 87 patients exhibited normal CRT, and 8 an abnormal one. Patients with abnormal CRT had an increased risk of adverse outcomes (88% vs. 20% p<0.001; RR 4.4 [2.7-7.4]), and hospital mortality (63% vs. 9% p<0.001; RR 6.7 [2.9-16]) as compared to those with normal CRT after FR. Specifically, CRT-normal patients required less frequently mechanical ventilation, renal replacement therapy, and ICU admission, and exhibited a lower hospital mortality. CONCLUSIONS: Hyperlactatemic sepsis patients with abnormal CRT after initial fluid resuscitation exhibit higher mortality and worse clinical outcomes than patients with normal CRT.

BACKGROUND.Abnormal central venous oxygen saturation (ScvO2) reflects an disbalance between oxygen demand and oxygen supply.In addition, weaning from mechanical ventilation by a spontaneous breathing trial (SBT) results in a significant increase in oxygen demand.Therefore, we hypothesized that the presence of low ScvO2 at the beginning of SBT would be a risk factor for weaning failure.METHODS.In a multicenter observational study, patients mechanically ventilated for more than 24h and clinically ready for a SBT were studied.Study variables were recorded at baseline, 2min, 30min, and at the end of the SBT.Decisions to extubate where taken by the attending physician based on their usual practice without knowledge of ScvO2 levels.Weaning failure was defined as a decision not to extubate at the end of the SBT, or reintubation within 48h after extubation.The baseline values of ScvO2 were categorized in quartiles.One-way ANOVA test and kruskal wallis test were used to analyze parametric and nonparametric continuous variables.A Chi-square test was used for qualitative variables.Multivariate regression analysis (corrected for the presence of a history of cardiac dysfunction) was used to find independent associations between ScvO2 and weaning failure.RESULTS.204 patients from 5 centers were included.Demographic and clinical characteristic are show in the Table 192.156 (76%) patients were successfully weaned.Of the patients that failed weaning (n = 48), 37 (77%) were not extubated at the end of the SBT, and 11 (23%) were reintubated within 48h.At baseline patients that failed to wean had lower central venous pressure, higher respiratory rate, and lower ScvO2 (Table 192).Sixty patients (29%) patients had a ScvO2 less than 70%.Multivariate regression analysis revealed the 25th quartile (ScvO2 = 63 +/- 4%) to be an independent risk factor for weaning failure OR 2.78 95% CI (1.09-7.08; P = 0.03).No other variables recorded were related to weaning failure.CONCLUSIONS.In a mixed group of critically ill patients ready for a SBT after at least 24h of mechanical ventilation, a low ScvO2 at the start of the SBT was an independent risk factor for a failure to wean